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Current Radiopharmaceuticals 2018Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA- 617 for therapy of metastatic castration-resistant prostate cancer have underlined the... (Review)
Review
BACKGROUND
Recent reports of the remarkable therapeutic efficacy of 225Ac-labeled PSMA- 617 for therapy of metastatic castration-resistant prostate cancer have underlined the clinical potential of targeted alpha therapy.
OBJECTIVE AND CONCLUSION
This review describes methods for the production of 225Ac and its daughter nuclide 213Bi and summarizes the current clinical experience with both alpha emitters with particular focus on recent studies of targeted alpha therapy of bladder cancer, brain tumors, neuroendocrine tumors and prostate cancer.
Topics: Actinium; Alpha Particles; Bismuth; Clinical Trials as Topic; Humans; Neoplasms; Radiochemistry; Radioimmunotherapy; Radioisotopes; Radiopharmaceuticals
PubMed: 29732998
DOI: 10.2174/1874471011666180502104524 -
Journal of Nuclear Medicine : Official... Sep 2018The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the...
The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts, which are present in more than 90% of epithelial carcinomas, including pancreatic, colon, and breast cancer. Cancer-associated fibroblasts feature high expression of fibroblast activation protein (FAP), which is not detectable in adult normal tissue but is associated with a poor prognosis in cancer patients. We developed an iodinated and a DOTA-coupled radiotracer based on a FAP-specific enzyme inhibitor (FAPI) and evaluated them in vitro using uptake, competition, and efflux studies as well as confocal microscopy of a fluorescence-labeled variant. Furthermore, we performed imaging and biodistribution studies on tumor-bearing animals. Finally, proof of concept was realized by imaging patients with Ga-labeled FAPI. Both FAPIs showed high specificity, affinity, and rapid internalization into FAP-expressing cells in vitro and in vivo. Biodistribution studies on tumor-bearing mice and on the first cancer patients demonstrated high intratumoral uptake of the tracer and fast body clearance, resulting in high-contrast images and negligible exposure of healthy tissue to radiation. A comparison with the commonly used radiotracer F-FDG in a patient with locally advanced lung adenocarcinoma revealed that the new FAP ligand was clearly superior. Radiolabeled FAPIs allow fast imaging with very high contrast in tumors having a high stromal content and may therefore serve as pantumor agents. Coupling of these molecules to DOTA or other chelators allows labeling not only with Ga but also with therapeutic isotopes such as Lu or Y.
Topics: Animals; Cancer-Associated Fibroblasts; Cell Line, Tumor; Cell Transformation, Neoplastic; Female; Gene Expression Regulation, Neoplastic; Humans; Kinetics; Ligands; Mice; Neoplasm Metastasis; Pancreatic Neoplasms; Positron-Emission Tomography; Radiochemistry
PubMed: 29626120
DOI: 10.2967/jnumed.118.210435 -
Scientific Reports Jan 2020Radioisotopes can be produced artificially from stable nuclei through the interaction with particles or highly energetic photons. In combination with modern detection...
Radioisotopes can be produced artificially from stable nuclei through the interaction with particles or highly energetic photons. In combination with modern detection and counting techniques, radioisotopes and radiochemical methods uniquely contribute to the health sciences. This Collection showcases salient aspects of medical radioisotope science ranging from the production, recovery and purification of radioisotopes to the methods used to attach them to biomolecules. The Collection also presents studies that highlight the importance of radiochemistry in the assessment of environmental radioactivity.
Topics: Humans; Radiochemistry; Radioisotopes
PubMed: 31924808
DOI: 10.1038/s41598-019-56278-1 -
Seminars in Nuclear Medicine May 2022After introduction of the first commercial combined PET and/or CT technology in 2001, this diagnostic tool quickly became a clinical success and was considered the... (Review)
Review
After introduction of the first commercial combined PET and/or CT technology in 2001, this diagnostic tool quickly became a clinical success and was considered the fastest growing diagnostic imaging technology ever. However, this technique is very dependent on the availability of positron emitting isotopes and radiochemistry to incorporate the radioactive isotopes into larger molecules of physiological interest. Within this review article a historical overview starting with the first applications of positron emitting isotopes in the 1930's is presented. Afterwards a more detailed presentation summarizing the physical basis and advancements in cyclotron technology is given. Radiochemical and/or pharmaceutical advancements are presented systematically for the most significant isotopes like O, N, C, F and Ga Besides these major PET isotopes, advancements of other radio-metals and future perspectives regarding application of new radionuclides will be discussed. Finally, very interesting new and compact accelerator technology and microfluidic chemical reaction approaches will be discussed. Especially, new compact accelerator technology might be new quantum leap within this radiodiagnostic technology and might result in even further prevalence, ultimately envisioned by the dose-on-demand concept that will be briefly discussed.
Topics: Cyclotrons; Humans; Positron-Emission Tomography; Radiochemistry; Radioisotopes; Radiopharmaceuticals
PubMed: 34836618
DOI: 10.1053/j.semnuclmed.2021.10.003 -
Nature Communications Jun 2023Positron emission tomography (PET) constitutes a functional imaging technique that is harnessed to probe biological processes in vivo. PET imaging has been used to... (Review)
Review
Positron emission tomography (PET) constitutes a functional imaging technique that is harnessed to probe biological processes in vivo. PET imaging has been used to diagnose and monitor the progression of diseases, as well as to facilitate drug development efforts at both preclinical and clinical stages. The wide applications and rapid development of PET have ultimately led to an increasing demand for new methods in radiochemistry, with the aim to expand the scope of synthons amenable for radiolabeling. In this work, we provide an overview of commonly used chemical transformations for the syntheses of PET tracers in all aspects of radiochemistry, thereby highlighting recent breakthrough discoveries and contemporary challenges in the field. We discuss the use of biologicals for PET imaging and highlight general examples of successful probe discoveries for molecular imaging with PET - with a particular focus on translational and scalable radiochemistry concepts that have been entered to clinical use.
Topics: Radiopharmaceuticals; Radiochemistry; Positron-Emission Tomography; Drug Development
PubMed: 37277339
DOI: 10.1038/s41467-023-36377-4 -
Bioconjugate Chemistry Nov 2023The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists... (Review)
Review
The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists to combine molecular subunits as if they were puzzle pieces. Over the last 25 years, the click chemistry toolbox has swelled from the canonical copper-catalyzed azide-alkyne cycloaddition to encompass an array of ligations, including bioorthogonal variants, such as the strain-promoted azide-alkyne cycloaddition and the inverse electron-demand Diels-Alder reaction. Without question, the rise of click chemistry has impacted all areas of chemical and biological science. Yet the unique traits of radiopharmaceutical chemistry have made it particularly fertile ground for this technology. In this update, we seek to provide a comprehensive guide to recent developments at the intersection of click chemistry and radiopharmaceutical chemistry and to illuminate several exciting trends in the field, including the use of emergent click transformations in radiosynthesis, the clinical translation of novel probes synthesized using click chemistry, and the advent of click-based pretargeting.
Topics: Click Chemistry; Radiochemistry; Azides; Radiopharmaceuticals; Cycloaddition Reaction; Alkynes
PubMed: 37737084
DOI: 10.1021/acs.bioconjchem.3c00286 -
Journal of Nuclear Medicine : Official... Aug 2023The worldwide proliferation of persistent environmental pollutants is accelerating at an alarming rate. Not surprisingly, many of these pollutants pose a risk to human... (Review)
Review
The worldwide proliferation of persistent environmental pollutants is accelerating at an alarming rate. Not surprisingly, many of these pollutants pose a risk to human health. In this review, we examine recent literature in which molecular imaging and radiochemistry have been harnessed to study environmental pollutants. Specifically, these techniques offer unique ways to interrogate the pharmacokinetic profiles and bioaccumulation patterns of pollutants at environmentally relevant concentrations, thereby helping to determine their potential health risks.
Topics: Humans; Environmental Pollutants; Radiochemistry; Molecular Imaging
PubMed: 37442598
DOI: 10.2967/jnumed.122.265209 -
The Journal of Biological Chemistry Nov 1969
Topics: Adrenochrome; Alkanes; Animals; Blood Proteins; Cattle; Centrifugation; Copper; Cytochromes; Epinephrine; Erythrocytes; Free Radicals; Hydrogen Peroxide; Oxidoreductases; Oxygen; Radiochemistry; Spectrophotometry; Xanthine Oxidase
PubMed: 5389100
DOI: No ID Found -
Molecular Imaging and Biology Feb 2022In oncology, biomarker research aimed to provide insights on cancer biology via positron emission tomography (PET) and single photon emission tomography (SPECT) imaging... (Review)
Review
In oncology, biomarker research aimed to provide insights on cancer biology via positron emission tomography (PET) and single photon emission tomography (SPECT) imaging has seen an incredible growth in the past two decades. Despite the increased number of publications on PET/SPECT radiopharmaceuticals, the field lacked standardization of in vitro and in vivo parameters necessary for the characterization of any radiotracer. Through the efforts of the World Molecular Imaging Society Education Committee, this white paper lays down validation studies that are essential to chemically and biologically characterize new radiopharmaceuticals derived from small molecules, peptides or proteins. Finally, a brief overview of the steps toward translation is also presented.Herein, we discuss the following: Chemistry and radiochemistry metrics to establish the identity of the imaging agent. In vitro and in vivo studies to examine the radiotracer's mechanism of action, which includes target specificity, pharmacokinetics and in vivo metabolism.
Topics: Medical Oncology; Positron-Emission Tomography; Radiochemistry; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon
PubMed: 34542804
DOI: 10.1007/s11307-021-01645-6 -
ChemistryOpen Jun 2022The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile... (Review)
Review
The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile techniques to introduce fluorine-18, especially for the radiolabelling of biologically or pharmacologically active molecules. Taking into consideration that the introduction of fluorine-18 (t =109.8 min) mostly proceeds under harsh conditions, radiolabelling of such molecules represents a challenge and is of enormous interest. Ideally, it should proceed in a regioselective manner under mild physiological conditions, in an acceptable time span, with high yields and high specific activities. Special attention has been drawn to 2-fluoroethyl and 3-fluoropropyl groups, which are often the active sites of radiofluorinated compounds. Precursors containing an ammonium leaving group - such as a strained azetidinium or aziridinium moiety - can help to overcome these obstacles leading to a convenient and mild introduction of [ F]fluoride with high radiochemical yields.
Topics: Ammonium Compounds; Positron-Emission Tomography; Radiochemistry; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 35736542
DOI: 10.1002/open.202200039